Anticholinergic drugs are among the most widely prescribed class of drugs today, used in the treatment of conditions from motion sickness to psychosis. Of the two 200 most prescribed drugs, a significant portion of them are Anticholinergic. I have limited the following studies to within the last two years, honestly because it was too depressing to dig any deeper.
Do Anticholinergic drugs cause dementia?:
Anticholinergic Drug Exposure and the Risk of DementiaA Nested Case-Control Study
There were significant increases in dementia risk for the anticholinergic antidepressants (adjusted OR [AOR], 1.29; 95% CI, 1.24-1.34), antiparkinson drugs (AOR, 1.52; 95% CI, 1.16-2.00), antipsychotics (AOR, 1.70; 95% CI, 1.53-1.90), bladder antimuscarinic drugs (AOR, 1.65; 95% CI, 1.56-1.75), and antiepileptic drugs (AOR, 1.39; 95% CI, 1.22-1.57) all for more than 1095 TSDDs.
Anticholinergic use for ≥3 months increased the risk of dementia on average by an estimated 46% versus nonuse. This relationship was consistent in studies assessing overactive bladder medications. The risk of developing dementia should be carefully considered in the context of potential benefit before prescribing anticholinergics.
This study confirmed the dose response relationship for cumulative anticholinergic burden measured using the Korean specific anticholinergic burden scale with incident dementia.
Anticholinergic drugs and the risk of dementia: A systematic review and meta-analysis
After pooling fourteen longitudinal and case-control studies with a total of 1,564,181 subjects, anticholinergic drug use was associated with an increased risk of all-cause dementia and Alzheimer’s disease. Both low and high anticholinergic drug burdens were associated with dementia. Moreover, there was a dose-dependent relationship between anticholinergic drugs and risk of dementia. With respect to the categories of anticholinergic drugs, antiparkinson, urological drugs, and antidepressants increased the risk for dementia; however, cardiovascular and gastrointestinal drugs played potentially protective roles.
Anticholinergic drug use, particularly long-term use, is associated with greater incidence of dementia and cognitive decline.
Anticholinergic medications and risk of dementia in older adults: Where are we now?
The review demonstrates moderate to strong risk of dementia with anticholinergic use in multiple studies involving older adults, irrespective of the study design, analytical approach, anticholinergic exposure and outcome definition. This risk is particularly significant with the cumulative burden and high-level anticholinergics. There also exists a dose-response relationship between anticholinergic use and increased risk for dementia. Therefore, anticholinergic agents can be considered as a modifiable risk factor for dementia and cognitive decline in older adults.
Are anticholinergics harmful to individuals with the conditions they are prescribed for?
Twenty-year effects of antipsychotics in schizophrenia and affective psychotic disorders
Participants with schizophrenia not on antipsychotics after the first 2 years have better outcomes than participants prescribed antipsychotics. Even when the confound by indication for prescribing antipsychotic medication is controlled for, participants with schizophrenia and affective psychosis do better than their medicated cohorts, strongly confirming the importance of exposing the role of aiDSP and antipsychotic drug resistance.
After adjustment for confounders, moderate and high cumulative exposure to antipsychotics within the first 5 years from FEP was consistently associated with a higher risk of adverse outcomes during the 19-year follow-up, as compared to low or zero exposure.
Cognitive burden of anticholinergic medications in psychotic disorders
Anticholinergic burden aggregated across all medications was inversely related to cognitive performance starting at ADS scores of 4 in participants with schizophrenia.
Long-term antipsychotic use was associated with greater cognitive decline and dementia progression in community-dwelling older adults with mild–moderate AD.
Anticholinergic Medication Burden–Associated Cognitive Impairment in Schizophrenia
Anticholinergic medication burden in schizophrenia is substantial, common, conferred by multiple medication classes, and associated with cognitive impairments across all cognitive domains. Anticholinergic medication burden from all medication classes–including psychotropics used in usual care–should be considered in treatment decisions and accounted for in studies of cognitive functioning in schizophrenia.
In conclusion, people with schizophrenia are exposed to severe ACB that can have a direct negative impact on functional capacity after controlling for its impact on cognition. Reducing ACB could improve functional capacity and potentially real-world function in schizophrenia.
Our analysis shows that anticholinergic burden reduces cognitive and daily living functions in patients with schizophrenia. A drug strategy with minimal anticholinergic burden may be helpful to patients if it does not adversely affect clinical symptoms.
The evidence supports association between increased ACB and future impairments in physical function and quality of life.
Consistency between anticholinergic burden scales in the elderly with fractures
The ACB scale identified the highest anticholinergic burden (26.8%) in prescriptions made the month before the fracture, and the highest agreement was between ACB and ADS (0.717); during hospitalization and at discharge, the cholinergic antagonists were best identified with ADS (77.7% and 72.1%, respectively), with the best agreement between ACB and ARS (0.613 and 0.568, respectively). The prescription of tramadol was found in 64.1% of hospitalized patients and in 61.4% of patients at the time of discharge.
Drugs with anticholinergic (antimuscarinic) properties are associated with cognitive impairment in individuals as young as 55 years, and only one such drug per day, regardless of its anticholinergic burden, is associated with both impaired cognition and impaired mobility in old-old adults. Therefore, wherever possible, clinicians should avoid prescribing drugs with anticholinergic properties.
This result suggests that the relationship between anticholinergic drug burden and fracture risk may differ depending on the anticholinergic burden scale used.
Anticholinergics May Carry Significant Cognitive and Gait Burden in Parkinson’s Disease
Patients with PD are exposed to significant anticholinergic burden from drugs prescribed for PD and non-PD indications. Higher anticholinergic burden is associated with cognitive impairment and FOG even in younger patients with PD.
Among patients with Parkinson’s disease in Taiwan, those with a high cumulative dose of anticholinergics had an increased risk of being diagnosed with dementia. Physicians should consider prescribing the lowest therapeutic dose of anticholinergic medication when making treatment decisions for patients with Parkinson’s disease.
Do anticholinergics cause delirium and increase mortality?: Effect of anticholinergic burden on treatment modification, delirium and mortality in newly diagnosed dementia patients starting a cholinesterase inhibitor: A population-based study
This study showed that high anticholinergic burden negatively affected the treatment response to cholinesterase inhibitors and that an average ACB score />/3 was an independent prognostic factor for delirium or mortality in dementia patients.
Autonomic nervous system dysfunction in schizophrenia: impact on cognitive and metabolic health
The strongest association of low heart rate variability was noted among patients on antipsychotic treatment with high-affinity muscarinic antagonism (i.e., clozapine, olanzapine and quetiapine).
Are doctors more wary about anticholinergics now that the risk of dementia is understood?:
Anticholinergic medication use is linked with increased cognitive decline, dementia, falls and mortality, and their use should be limited in older people. Use of potent anticholinergic medications nearly doubled in England’s older population over 20 years with some of the greatest increases amongst those particularly vulnerable to anticholinergic side-effects.
Increase in anticholinergic burden from 1990 to 2015: Age-period-cohort analysis in UK biobank
Anticholinergic burden in the sample increased up to 9-fold over 25 years and was observed for both period and age effects across most classes of drugs. The greatest increase was seen in the prescribing of antidepressants. Female sex, lower education and greater deprivation were associated with greater anticholinergic burden.
Are medical professionals aware of the risk of anticholinergic drugs?:
A total of 74% participants admitted to have no understanding of the term ACB, 48% participants prescribe anticholinergics in their daily role, 44% knew that cognition was adversely affected by anticholinergics, and 16% participants were aware of scoring system. Only 16% participants routinely counsel women of cognitive side effects when anticholinergics are started. 86% reported that they would avoid prescribing medications which might affect cognition if possible. If given choice as a patient, 94% would avoid these medications if they were informed of the specific side effects like impaired cognition, physical decline, falls, hospital admissions and increased mortality.
Are anticholinergic prescriptions being adequately screened for interactions?:
In a representative sample of outpatient visits, polypharmacy was extremely common among PWD, driven by a wide array of medication categories.
Inappropriate medication prescriptions are associated with impaired physical function across longitudinal and cross-sectional studies in older adults situated in diverse settings.
An overview of prevalence, determinants and health outcomes of polypharmacy
Our review showed that the prevalence of polypharmacy varied between 10% to as high as around 90% in different populations. Chronic conditions, demographics, socioeconomics and self-assessed health factors were independent predictors of polypharmacy. Polypharmacy was reported to be associated with various adverse outcomes after adjusting for health conditions.
Is there a consistent way to determine risk from Anticholinergic drugs?
Consistency between anticholinergic burden scales in the elderly with fractures
The scales evaluated show marked discrepancies between them, with highly variable frequencies of anticholinergic drugs identified at the different prescription times, and with low agreement among them, which is why the scales are not interchangeable in patients with bone fractures.
Anticholinergic Drug Burden and Delirium: A Systematic Review
ADB assessed with the ARS is consistently associated with delirium.
Are Anticholinergic drugs effective treatments?:
The 20-year data indicate that, longitudinally, after the first few years, antipsychotic medications do not eliminate or reduce the frequency of psychosis in schizophrenia, or reduce the severity of post-acute psychosis, although it is difficult to reach unambiguous conclusions about the efficacy of treatment in purely naturalistic or observational research. Longitudinally, on the basis of their psychotic activity and the disruption of functioning, the condition of the majority of SZ prescribed antipsychotics for multiple years would raise questions as to how many of them are truly in remission.